| Texto completo | |
| Autor(es): |
Geraldo, Murilo Vieira
;
Nakaya, Helder Imoto
;
Kimura, Edna Teruko
Número total de Autores: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ONCOTARGET; v. 8, n. 6, p. 9597-9607, 2017. |
| Citações Web of Science: | 9 |
| Resumo | |
Papillary thyroid carcinoma (PTC) is the most prevalent malignant neoplasia of the thyroid gland. A fraction of PTC cases show loss of differentiation and aggressive behavior, with radioiodine therapy resistance and metastasis. Although microRNAs (miRNAs) emerged as promising molecular markers for PTC, their role in the loss of differentiation observed during PTC progression remains to be fully understood. We performed the large-scale analysis of miRNA expression during PTC progression in BRAFT1799A-transgenic animals (Tg-Braf) and thyroid cancer cell lines and identified the marked downregulation of several miRNAs from the region 14q32. Data from The Cancer Genome Atlas (TCGA) confirmed the global downregulation of miRNAs from the 14q32 region in human PTC. The regulatory network potentially suppressed by these miRNAs suggests that key cancer-related biological processes such as cell proliferation, adhesion, migration and angiogenesis. Among the downregulated miRNAs, we observed that miR-654-3p levels decrease with long-term PTC progression in Tg-Braf mice and inversely correlate with EMT. The in vitro restoration of miR-654-3p decreased cell proliferation and migration and induced reprogramming of metastasis-related genes, suggesting a tumor suppressor role for this miRNA. In conclusion, we show global downregulation of 14q32-encoded miRNAs in an in vivo model of PTC progression. The potential circuitry in which these miRNAs are involved suggests that these miRNAs could play a key role in the pathophysiology of PTC and therefore be relevant for the development of new therapeutic strategies. (AU) | |
| Processo FAPESP: | 11/50732-2 - Perfil de expressoes de micrornas na oncogenese tiroidiana: papel da regulacao pos-transcricional na progressao tumoral e influencia do iodo. |
| Beneficiário: | Edna Teruko Kimura |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 11/52051-2 - Microtranscriptoma da oncogênese tireoideana: regulação pós-transcricional na tumorigênese e progressão do câncer de tireoide |
| Beneficiário: | Murilo Vieira Geraldo |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |